Dalila Pinto, et al., Functional impact of global rare copy number variation in autism spectrum disorders, doi:10.1038/nature09146
Here we analyzed the genome-wide characteristics of rare (<1% frequency) copy number variation in ASD using dense genotyping arrays.
We also discovered an enrichment of CNVs disrupting functional gene sets involved in cellular proliferation, projection and motility, and GTPase/Ras signalling.
After eliminating CNVs that are less likely to have an etiological role, 25 CNVs remained in the ASD group, compared to only four in the controls. Moreover, the latter four CNVs were all duplications at 1q21.1, 16p11.2 or 22q11.2, loci known to exhibit incomplete penetrance and variable expressivity.
We identified enrichments in gene sets known to be involved in ASDs and also discovered new candidate ASD pathways.
We further assessed the relationship of our functional enrichment map with known ASD/intellectual disability genes and found genes enriched in sets linked to microtubule cytoskeleton, glycosylation and CNS development/adhesion.